A new drug that moderately slows the progression of Alzheimer’s disease is poised to be approved by US regulators this week, providing a glimmer of hope to people with the most common form of dementia despite questions about its safety, potential cost, and availability.
For Cambridge-based Biogen, codeveloper of the experimental medicine, an approval could help the firm repair its reputation, which was marred by the disastrous rollout of another Alzheimer’s drug it helped create.
On Thursday, two congressional committees said the Food and Drug Administration’s review and 2021 approval of the earlier drug, Aduhelm, was “rife with irregularities,” including dozens of undisclosed calls and e-mails with Biogen that reflected an “inappropriate” level of coordination between the drugmaker and regulators. The congressional report also said Biogen tried to maximize its potential profit at the expense of patients and taxpayers when it priced the drug at $56,000 a year.
The new drug, called lecanemab, is far less controversial. Although it doesn’t reverse or even stop Alzheimer’s, Biogen and its Japanese codeveloper, Eisai, recently found that the therapy slowed cognitive decline by 27 percent over an 18-month study of people in the early stages of dementia. The companies also collaborated on Aduhelm, but Eisai is taking the lead on lecanemab in dealing with the FDA this time.
Despite lecanemab’s relatively modest benefits, many neurologists are heralding it as one of the biggest advances in Alzheimer’s treatment in nearly two decades — maybe ever. Experts are hopeful the drug will mark a turning point and that administering lecanemab before symptoms arise or combining it with other treatments could further stall or maybe even prevent the disease.
“This is the first time that I have been convinced that a drug designed to slow down Alzheimer’s disease actually does that,” said Dr. Andrew E. Budson, chief of cognitive and behavioral neurology at the Veterans Affairs Boston Healthcare System. “It’s surprising, but it looks like it works.”
Despite winning FDA approval, Aduhelm was snubbed by health systems and insurers amid safety concerns, criticism of its initial price tag, and fierce debate over whether the medication helped slow dementia. The controversy culminated last spring when Medicare said it wouldn’t cover the drug for most patients and Biogen’s embattled chief executive stepped down.
Lecanemab will have to overcome some similar concerns.
Media reports have linked the drug to at least three deaths in recent months. Scientists struggle to translate what a 27 percent slowing of disease would mean for patients and their families. And unless a previous Medicare ruling is overturned, lecanemab won’t be covered for most people until regulators conduct a more thorough review of the drug.
Dr. Sam Gandy, an Alzheimer’s expert and professor of neurology and psychiatry at the Mount Sinai Health System in New York, which opted not to administer Aduhelm to patients, predicted the FDA will focus more on the deaths of the three patients in the trial than on the congressional findings about the earlier drug.
“It certainly will be discussed, but I don’t think it will ultimately torpedo approval,” he said of the committees’ report. “I think lecanemab deserves to be treated differently.”
The preliminary results from the trial of nearly 1,800 people with mild cognitive impairment or mild Alzheimer’s were announced in late September and described fully in late November. To many scientists’ relief, those detailed results held few surprises and helped confirm that the drug’s effects are real.
“Actually seeing the data was really exciting,” said Robert J. Vassar, director of the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease at Northwestern University Feinberg School of Medicine. “It’s a modest effect, but it’s really remarkable that it’s statistically significant.”
People who got lecanemab scored 0.45 points better on an 18-point scale measuring cognitive decline, compared to placebo recipients. Eisai estimates that modest effect could translate into slowing the disease by 7.5 months, and possibly four or five times longer as patients take the drug over several years.
But experts say that difference might not be readily noticeable by patients and their families.
“How that translates into kind of day-to-day activities is not entirely clear,” said Dr. Brian Silver, vice chair of neurology clinical operations at UMass Memorial Medical Center.
Lecanemab is the latest in a long line of drugs designed to remove a sticky protein called amyloid beta from the brain, where its accumulation is linked to Alzheimer’s. Scientists say that similar drugs may have failed because they were tested in people with moderate or advanced disease, when removing amyloid is too little too late.
“People already have amyloid in their brains for over a decade by the time they have substantial symptoms,” said Dr. Reisa Sperling, director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital. She thinks even the lecanemab study was not treating patients early enough, “but I feel that we’re on the right path.”
Sperling is leading a large clinical trial, sponsored by Biogen, Eisai, and the National Institutes of Health, to test lecanemab in patients who aren’t yet showing signs of dementia but have evidence of amyloid accumulation on their brains scans. The hope is that earlier treatment can further delay or even prevent Alzheimer’s. Results from the trial, which will follow patients for four years, are expected in 2027.
Another study, led by researchers at Washington University in St. Louis, will combine lecanemab with an experimental Alzheimer’s therapy that cleans up another problematic protein called tau that’s also implicated in the disease.
“The goal here is to try to treat people before they get sick,” said Dr. Randall J. Bateman, the Washington University neurologist leading the study. “Once people are symptomatic, we don’t believe that removing amyloid alone will be a cure.”
Much as oncologists combine different drugs to create treatments that target a patient’s unique form of cancer, experts anticipate that the future of Alzheimer’s treatment will pair amyloid-busting drugs like lecanemab with other still-experimental medicines that remove tau or dampen inflammation in the brain.
“We’re going to need an arsenal of drugs for what’s essentially personalized medicine,” said Diane Bovenkamp, chief scientist of the BrightFocus Foundation, a nonprofit organization that funds Alzheimer’s research.
Yet safety concerns over amyloid-lowering medicines could cast a pall on such ambitions. Aduhelm and lecanemab both caused potentially dangerous brain bleeding and swelling in some recipients. Although the rates were lower for lecanemab, scientists expect there will be debate about whether it is safe enough.
Some neurologists, including the VA’s Budson, believe that the drug’s side effects can be managed in most patients, but that risks need to be better understood. Budson also noted that brain swelling and bleeding was more common in people who carry two copies of a gene called APOE4, which increases the chance of developing Alzheimer’s.
“I think I would have a different conversation with them,” he said.
Access to lecanemab may be limited initially as debate over its safety plays out. The drug is up for what’s known as accelerated approval by the FDA based on its ability to remove amyloid from the brain. After Aduhelm got a similar approval in 2021, the Centers for Medicare and Medicaid Services said it would only pay for such amyloid-busting drugs after the FDA granted full approval based on evidence that they actually helped slow the disease.
Eisai plans to complete its submission for full approval early this year, but it could take the FDA most of the year to make its decision.
Advocacy groups including the Alzheimer’s Association have renewed their protest over that CMS decision in light of lecanemab’s positive data. The organization estimates that more than 2,000 people progress from mild dementia — which is what lecanemab was designed to treat — to more advanced disease every day.
“The current CMS policy to severely limit access to these treatments eliminates people’s options, is resulting in continued irreversible disease progression, and contributes to greater health inequities,” Joanne Pike, Alzheimer’s Association president and incoming chief executive officer, said in a public statement.
Ivan Cheung, the chairman and chief executive of Eisai’s US operations recently told the Globe that Eisai has been in discussions with CMS for several months and hopes that data from its advanced clinical study will persuade the agency to reconsider its decision.
Another point of contention over the drug could be its price, which isn’t disclosed yet. Cheung said Eisai plans “to provide a detailed explanation” of lecanemab’s price after it is approved.
Last month, the Institute for Clinical and Economic Review, a Boston drug-pricing watchdog, released a 184-page draft report concluding that lecanemab could be considered cost-effective if priced between $8,500 to $20,600 per year.
That range is higher than the $2,500 to $8,300 price it dubbed “fair” for Aduhelm, but considerably less than the initial $56,000 price tag for the drug — which Biogen later halved to $28,000.
Analysts estimate lecanemab could generate sales of $8 billion a year, with profits split between Biogen and Eisai. The firms’ stocks are up about 40 percent and 60 percent, respectively, since the positive lecanemab data were first announced in late September.
Jonathan Saltzman of the Globe staff contributed to this report.
Ryan Cross can be reached at email@example.com. Follow him on Twitter @RLCscienceboss.